Astro City is a mecca for super-powered beings, largely because Air Ace, the first public super-hero and a decorated veteran, established residency there after World War I. The series has established a large cast of characters, from small cameo roles of a few panels to full center stage attention spanning several issues.

The series is an anthology that focuses on different characters living within Astro City, using a wide range of viewpoints. Some issues are told from the viewpoint of heroes, some from the more typical vantage point of average people, others from villains and shady criminals.